In a case where a human tissue or organ such as a nerve or tendon is injured due to an accident, disaster or disease and the injury cannot be cured by self-recovery of a patient, a disorder occurs in perception, sensation, mobility or the like. For such a patient, with the development of a technology for connecting injured areas under a microscope in recent years, therapeutics such as surgical suturing for connecting cut portions or nerve autotransplantation, by which a nerve or tendon of a patient himself or herself biopsied from another part of the body is transplanted to recover the lost function, has been effective.
However, when the injured region is too large, restoration by the above-mentioned connection is impossible and it has been necessary to obtain a nerve from another location where a disorder, if any, could be believed to be less important than the disorder of the injured portion of concern and transplant it to the injured portion. In this case, although it is less important than the disorder at the portion where injury first occurred, the nerve at another location that has received no injury and is healthy is biopsied, resulting in a disorder in perception, sensation or mobility being generated at that location.
As one example of nerve autotransplantation, there may be mentioned one including, first, a biopsy of a sura nerve and then transplanting of the nerve to an injured location. In this case, the problem is that usually skin sensation, etc. of the area from ankle to instep is lost. Accordingly, there has been a keen demand for a therapeutic method that enables restoration of the injured area without causing any impediment to another area (ankle, etc.).
To overcome the drawbacks of nerve autotransplantation, various studies have been made with a view to recovery of original functions by substituting an injured area with an artificial instrument. For example, attempts have been made in which a ruptured portion of a nerve is covered by a tubular structure (also called a covering material) made of a nonabsorbable material which is not absorbed by the human body (silicon compounds, fluorine compounds and various synthetic polymers) with the expectation of growth and proliferation of new nerve cells from the cut nerve in the tubular member so that the cut nerve portion can be grafted again. (Ducker et al., Journal of Neurosurgery, 28, 582-587 (1968); Midgler et al., Surgical Forum, 19, 519-528 (1968); Lundborg et al., Journal of Neuropathology in Experimental Neurology, 41, 412-422 (1982); Molander et al., Muscle & Nerve, 5, 54-58 (1982); Uzman et al., Journal of Neuroscience Research, 9, 325-338 (1983); Nyilas et al., Transactions American Society of Artificial Internal Organs, 29, 307-313 (1983); U.S. Pat. No. 4,534,349, etc.)
In these experiments, although some cell proliferation is observed at the both ends of the cut nerve, no recovery by grafting the cut nerve is attained. The reason for this is that when cells proliferate, generally they adhere to the tubular structure. From this position they proliferate in such a direction that they cover the cut portion but mere covering of the cut portion leaves a gap between the cut ends and proliferation of cells is terminated before the cells completely fill the cut portion, so that restoration of the cut gap is not achieved.
Also, since the implanted tubular structure (also called a covering material) is artificially synthesized, it exists as a foreign matter in the body forever, which is undesirable. Accordingly, to overcome the problem of the residual foreign matter, there is an example in which such a tubular structure is substituted by a bioabsorbable material (Suzuki et al., Artificial Organs, 27(2), 490-494 (1998)). Although use of a bioabsorbable material for the tubular structure solves the problem of residual foreign matter in the body, the problem of the existence of a gap still remains to be solved and it has been difficult to restore the deficit portion by cell proliferation.
Furthermore, to solve the problem of a gap inside the tubular structure made of a bioabsorbable material, an attempt has been made in which a fiber bundle of collagen is inserted and coated with fibronectin (FN) (Japanese Patent Application Laid-open No. Hei 5-237139, Hiroki Shimada, et al., Artificial Organ, 22(2), 359-363, 1993). In this case, although the problem of the residual foreign matter in the body and the problem of the existence of a gap may be solved, the following problems still remain. That is, the collagen fiber bundle is thin and tends to be cut so that it is difficult to handle it and also it is difficult to insert it in a tubular structure such that it fully fills the inside of the tubular structure. If the filling amount of the fiber bundle is decreased in order to facilitate insertion, there occur various defects that the gap between the fibers increases, the fiber bundle cannot be fixed well, localization of the fiber bundle inside the tubular member occurs and so on. Therefore, both cases are undesirable since the gap inside is increased, giving the same results as those of the case where the above-mentioned gap is large.
Also, in the case where the filling amount of the fiber bundle is increased, other problems remain. That is, when the collagen fiber is filled so that there can occur no localization of the fiber in the inside of the tubular structure, the filling ratio of the lumen of the tubular structure increases but the space for cell proliferation become narrow. Furthermore, in order for cells to efficiently proliferate, nutrients that the cells need must be quickly supplied and waste products generated by metabolism must be quickly removed. However, when the fiber bundle is inserted in a high filling density, exchange of substances is more inhibited closer to the central portion of the fiber bundle, so that it cannot be said that the environment is suitable for cell proliferation and, therefore, the fiber bundle is not suitable for restoring the nerve by cell proliferation.
Also, as a means for providing more efficient cell proliferation, a tubular structure encapsulating therein a cell growth factor has been reported (U.S. Pat. No. 4,963,146). In addition, a tubular structure coated on the surface of the lumen with fibrinogen, fibronectin or the like (Non-toxic Nerve Guide Tubes Support Neovascular Growth in Transected Rat Optic Nerve, R. Madison et al., Experimental Neurology, 86(3): 448-461, 1984), a tubular structure filled in the lumen thereof with fiber coated with laminin (Japanese Patent Application Laid-open No. Hei 5-237139, Hiroki Shimada, et al., Artificial Organ, 2:2(2), 359-363, 1993) and the like are known. However, when a growth factor or the like is coated on the surface of the lumen, the surface area is limited and the cell growth factor does not reach cells remote from the coated wall surface since the cells proliferate three-dimensionally. Also, when the cell growth factor is coated on the fiber filling the lumen, although the coating surface area is larger than the surface area of the lumen, the amount of the cell factor with respect to the volume of the lumen decreases because of the volume of the filled fiber.